Hepatitis B surface antigen clearance in HIV/HBV-coinfected patients: associated clinical factors and a rare amino acid substitution underlying occult infection
- 1Kumamoto University Hospital
Abstract
BackgroundHBV coinfection is more common among people with HIV than in the general population. Nucleotide reverse transcriptase inhibitors (NRTIs) in antiretroviral therapy (ART) are also active against HBV. Growing use of NRTI-sparing regimens raises concern about HBV reactivation.
ObjectivesTo determine the rate, cumulative incidence, and factors associated with HBsAg clearance in HIV/HBV-coinfected patients, and to characterize the genetic/structural basis of occult HBV infection (OBI) in the same cohort.
Study designWe retrospectively reviewed 256 people with HIV at Kumamoto University Hospital in Japan (1986-2025), stratified by HBsAg clearance status; clinical factors were compared and cumulative incidence estimated by Kaplan-Meier analysis. OBI cases underwent HBsAg-region sequencing.
ResultsFifteen patients were analyzed (12 HBsAg-positive, 3 OBI). HBsAg clearance occurred in 7/12 (58%). The Kaplan-Meier estimated cumulative incidence reached 25% by 2 years and 64.3% at approximately 4.4 years, after which no additional clearance events were observed during follow-up. Clearance was associated with higher CD4 ([≥] 200 cells/L: 71% vs 0%) and lower HIV-RNA (<105 copies/mL: 86% vs 20%); HBV-DNA was significantly higher in the clearance group than OBI (adjusted p = 0.007). All OBI sequences matched genotype C2; one also carried a rare genotype A2 a determinant substitution, N131K (0.23% of genotype A sequences in HBVdb).
ConclusionsHBsAg clearance was frequent, concentrated within 3-4 years of ART, and associated with preserved immune status and HBV replicative activity. A rare a determinant substitution may cause false-negative HBsAg in OBI, informing NRTI-sparing ART selection.
HighlightsO_LINo further HBsAg clearance events were observed after approximately 4.4 years. C_LIO_LIHigher CD4 count and lower HIV-RNA at baseline were associated with HBsAg clearance. C_LIO_LIHBV-DNA was significantly higher in HBsAg-clearance patients than in OBI patients. C_LIO_LIA rare a determinant substitution (N131K) was found in one occult infection case. C_LIO_LIIn silico modeling suggested that N131K may perturb HBsAg-antibody binding affinity through altered loop dynamics, not direct epitope disruption. C_LI
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BibTeX
@misc{takabayashi2026hepatitis,
title = {{Hepatitis B surface antigen clearance in HIV/HBV-coinfected patients: associated clinical factors and a rare amino acid substitution underlying occult infection}},
author = {M. Takabayashi and T. Nakamura and H. Nakata and J.-i. Yasunaga and S. Matsushita},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.02.26362028},
url = {https://www.medrxiv.org/content/10.64898/2026.09.02.26362028v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Hepatitis B surface antigen clearance in HIV/HBV-coinfected patients: associated clinical factors and a rare amino acid substitution underlying occult infection
AU - M. Takabayashi
AU - T. Nakamura
AU - H. Nakata
AU - J.-i. Yasunaga
AU - S. Matsushita
PY - 2026
DA - 2026/09/02
PB - medRxiv
DO - 10.64898/2026.09.02.26362028
UR - https://www.medrxiv.org/content/10.64898/2026.09.02.26362028v1
AB - BackgroundHBV coinfection is more common among people with HIV than in the general population. Nucleotide reverse transcriptase inhibitors (NRTIs) in antiretroviral therapy (ART) are also active against HBV. Growing use of NRTI-sparing regimens raises concern about HBV reactivation. ObjectivesTo determine the rate, cumulative incidence, and factors associated with HBsAg clearance in HIV/HBV-coinfected patients, and to characterize the genetic/structural basis of occult HBV infection (OBI) in the same cohort. Study designWe retrospectively reviewed 256 people with HIV at Kumamoto University Hospital in Japan (1986-2025), stratified by HBsAg clearance status; clinical factors were compared and cumulative incidence estimated by Kaplan-Meier analysis. OBI cases underwent HBsAg-region sequencing. ResultsFifteen patients were analyzed (12 HBsAg-positive, 3 OBI). HBsAg clearance occurred in 7/12 (58%). The Kaplan-Meier estimated cumulative incidence reached 25% by 2 years and 64.3% at approximately 4.4 years, after which no additional clearance events were observed during follow-up. Clearance was associated with higher CD4 ([≥] 200 cells/L: 71% vs 0%) and lower HIV-RNA (<105 copies/mL: 86% vs 20%); HBV-DNA was significantly higher in the clearance group than OBI (adjusted p = 0.007). All OBI sequences matched genotype C2; one also carried a rare genotype A2 a determinant substitution, N131K (0.23% of genotype A sequences in HBVdb). ConclusionsHBsAg clearance was frequent, concentrated within 3-4 years of ART, and associated with preserved immune status and HBV replicative activity. A rare a determinant substitution may cause false-negative HBsAg in OBI, informing NRTI-sparing ART selection. HighlightsO_LINo further HBsAg clearance events were observed after approximately 4.4 years. C_LIO_LIHigher CD4 count and lower HIV-RNA at baseline were associated with HBsAg clearance. C_LIO_LIHBV-DNA was significantly higher in HBsAg-clearance patients than in OBI patients. C_LIO_LIA rare a determinant substitution (N131K) was found in one occult infection case. C_LIO_LIIn silico modeling suggested that N131K may perturb HBsAg-antibody binding affinity through altered loop dynamics, not direct epitope disruption. C_LI
ER -